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Hamulyák EN, Wiegers HMG, Scheres LJJ, et al. Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study. Res Pract Thromb Haemost. 2020;5(1):223-230doi: 10.1002/rth2.12471.
Hamulyák, E. N., Wiegers, H. M. G., Scheres, L. J. J., Hutten, B. A., de Lange, M. E., Timmermans, A., Westerweel, P. E., Nijziel, M. R., Kruip, M. J. H. A., Ten Wolde, M., Ypma, P. F., Klok, F. A., Nieuwenhuizen, L., van Wissen, S., Hovens, M. M. C., Faber, L. M., Kamphuisen, P. W., Büller, H. R., & Middeldorp, S. (2021). Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study. Research and practice in thrombosis and haemostasis, 5(1), 223-230. https://doi.org/10.1002/rth2.12471
Hamulyák, Eva N, et al. "Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study." Research and practice in thrombosis and haemostasis vol. 5,1 (2021): 223-230. doi: https://doi.org/10.1002/rth2.12471
Hamulyák EN, Wiegers HMG, Scheres LJJ, Hutten BA, de Lange ME, Timmermans A, Westerweel PE, Nijziel MR, Kruip MJHA, Ten Wolde M, Ypma PF, Klok FA, Nieuwenhuizen L, van Wissen S, Hovens MMC, Faber LM, Kamphuisen PW, Büller HR, Middeldorp S. Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study. Res Pract Thromb Haemost. 2020 Dec 18;5(1):223-230. doi: 10.1002/rth2.12471. eCollection 2021 Jan. PMID: 33537547; PMCID: PMC7845056.
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Res Pract Thromb Haemost. 2020 Dec 18;5(1):223-230. doi: 10.1002/rth2.12471. eCollection 2021 Jan.

Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study.

Research and practice in thrombosis and haemostasis

Eva N Hamulyák, Hanke M G Wiegers, Luuk J J Scheres, Barbara A Hutten, Maria E de Lange, Anne Timmermans, Peter E Westerweel, Marten R Nijziel, Marieke J H A Kruip, Marije Ten Wolde, Paula F Ypma, Frederikus A Klok, Laurens Nieuwenhuizen, Sanne van Wissen, Marcel M C Hovens, Laura M Faber, Pieter W Kamphuisen, Harry R Büller, Saskia Middeldorp

Affiliations

  1. Department of Vascular Medicine Amsterdam UMC Amsterdam Cardiovascular Sciences University of Amsterdam Amsterdam The Netherlands.
  2. Department of Internal Medicine Radboud University Medical Center Nijmegen The Netherlands.
  3. Department of Clinical Epidemiology, Biostatistics and Bioinformatics Amsterdam UMC Amsterdam Cardiovascular Sciences University of Amsterdam Amsterdam The Netherlands.
  4. Department of Gynecology and Obstetrics Amsterdam UMC University of Amsterdam Amsterdam The Netherlands.
  5. Department of Internal Medicine Albert Schweitzer Hospital Dordrecht The Netherlands.
  6. Department of Hematology Catharina Hospital Eindhoven Eindhoven The Netherlands.
  7. Department of Hematology Erasmus University Medical Centre Rotterdam The Netherlands.
  8. Department of Internal Medicine Flevo Hospital Almere The Netherlands.
  9. Department of Hematology Haga Hospital The Hague The Netherlands.
  10. Department of Thrombosis and Haemostasis Leiden University Medical Centre Leiden The Netherlands.
  11. Department of Internal Medicine Máxima Medical Centre Veldhoven The Netherlands.
  12. Department of Internal Medicine OLVG Amsterdam The Netherlands.
  13. Department of Internal Medicine Rijnstate Hospital Arnhem The Netherlands.
  14. Department of Internal Medicine Red Cross Hospital Beverwijk The Netherlands.
  15. Department of Internal Medicine Tergooi Hospital Hilversum The Netherlands.

PMID: 33537547 PMCID: PMC7845056 DOI: 10.1002/rth2.12471

Abstract

BACKGROUND: In premenopausal women, treatment with direct oral factor Xa inhibitors is associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists (VKA). Treatment with the direct oral thrombin inhibitor dabigatran appears to be associated with a reduced risk of HMB compared with VKA. These findings come from small observational studies or post hoc analyses of trials in which HMB was not a primary outcome. Use of tranexamic acid during the menstrual period may be effective in patients with HMB, but prospective data regarding efficacy and safety in patients on anticoagulant treatment are lacking.

RATIONALE AND DESIGN: A direct comparison of a factor Xa inhibitor and a thrombin inhibitor with HMB as primary outcome, as well as an evaluation of the effects of adding tranexamic acid in women with anticoagulant-associated HMB is highly relevant for clinical practice. The MEDEA study is a randomized, open-label, pragmatic clinical trial to evaluate management strategies in premenopausal women with HMB associated with factor Xa inhibitor therapy.

OUTCOMES: Women using factor Xa inhibitors with proven HMB, as assessed by a pictorial blood loss assessment chart (PBAC) score of >150, will be randomized to one of three study arms: (i) switch to dabigatran; (ii) continue factor Xa inhibitor with addition of tranexamic acid during the menstrual period; or (iii) continue factor Xa inhibitor without intervention. The primary outcome is the difference in PBAC score before and after randomization. Here, we present the rationale and highlight several unique features in the design of the study.

© 2020 Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).

Keywords: dabigatran; factor Xa inhibitors; menorrhagia; prospective studies; tranexamic acid

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